Using floating gate field effect transistors for chemical and/or biological sensing

ABSTRACT

Specific ionic interactions with a sensing material that is electrically coupled with the floating gate of a floating gate-based ion sensitive field effect transistor (FGISFET) may be used to sense a target material. For example, an FGISFET can use (e.g., previously demonstrated) ionic interaction-based sensing techniques with the floating gate of floating gate field effect transistors. The floating gate can serves as a probe and an interface to convert chemical and/or biological signals to electrical signals, which can be measured by monitoring the change in the device&#39;s threshold voltage, V T .

§0. RELATED APPLICATIONS

This application is a divisional application of U.S. patent applicationSer. No. 11/033,046 (the entire contents of which are incorporatedherein by reference), titled “FLOATING GATE FIELD EFFECT TRANSISTORS FORCHEMICAL AND/OR BIOLOGICAL SENSING,” filed on Jan. 11, 2005, listingKalle LEVON, Arifur RAHMAN, Tsunehiro SAI and Ben ZHAO as the inventors,and scheduled to issue as U.S. Pat. No. 7,462,512 on Dec. 9, 2008.

§1. BACKGROUND

§1.1 Field of the Invention

The present invention concerns biological and/or chemical sensing. Inparticular, the present invention concerns floating gate (e.g., siliconor organic) transistors, such as Ion Sensitive Field Effect Transistors(ISFETs) for example, for chemical and/or biological sensing.

§1.2 Background Information

The key element of a conventional silicon-based ISFET is a gatecapacitor formed between the gate and substrate. The electric fieldwithin the gate (or oxide) capacitor is determined by the difference inwork function of the plate materials forming the gate and siliconsubstrate. The electric field within the gate oxide determines theamount of surface charge near the silicon and oxide interface and setsthe conductivity of the field effect transistor (FET) (between sourceand drain).

If the gate of an ISFET is formed by a material which is sensitive toselective gases or analytes, the electric field within gate oxide willbe determined by the electrochemical properties of the combined (gateand gas or analyte) system. This mechanism has been exploited to designvarious types of silicon based ISFETs. (See, e.g., C. G. Jakobson, U.Dinnar, M. Feinsod, and Y. Nemirovsky, “Ion-Sensitive Field-EffectTransistors in Standard CMOS Fabrication by Post Processing,” IEEESensors Journal, (2002); and J. Janata, “Electrochemical Microsensors,”Proceedings of the IEEE, Vol. 91(6), pages 864-869 (2003), bothincorporated herein by reference.)

FIG. 1 depicts a conventional ion sensitive field effect transistor(ISFET) submerged in gas or analyte. Specifically, silicon based ISFET120 comprising a gate 130, a source 124, a drain 126, a silicon oxidelayer 128, and a silicon substrate 122 is exposed to a sample (gas oranalyte) in a container 110 with a reference electrode 140 so as todetect the presence and/or amount or concentration of a target in thesample.

Although conventional Si-based ISFETs can sense various types oftargets, there are some limitations that prevent their widespreaddeployment. For example, in a conventional scheme for ISFET-basedsensing, such as that shown in FIG. 1, the gate 130 voltage is set bythe electro-chemical properties of the sensing material and the biasvoltage of a reference electrode 140. Due to this referenceelectrode-based biasing scheme, these ISFETs are suitable as pH sensors,but they have limited use as gas sensors.

To overcome some of these limitations, the electrical properties of theconductive channel of ISFETs can be modulated directly, without theintervention of gate electrode, as shown in FIG. 2. FIG. 2 depicts aconducting polymer-based ISFET 210 exposed to gas or analyte.Specifically, an organic-based ISFET 210 comprises a gate 220, a source214, a drain 216, an oxide layer 218, and a conducting polymer substrate212 (which includes conductive channel from source 214 to drain 216).This ISFET 210 may be exposed to a sample (gas or analyte) so as todetect the presence and/or amount or concentration of a target in thesample. Although the use of conducting polymer-based ISFETs simplifiesthe sensing measurements, only those ISFETs having a conducting polymeras the channel/substrate material have shown promising results.Unfortunately, organic FETs generally have a much lower drive currentcompared to bulk silicon devices. Consequently, a comparatively large(e.g., high device width/length ratio) device is required for acceptabledrive current to suppress the affect of background noise and to minimizethe need for significant amplification of the detected signal. It isalso difficult to integrate on-chip bias and peripheral circuits withorganic FETs, and they are not as easily miniaturizable as silicon FETs.

In view of the foregoing disadvantages of known transistor-basedsensors, it would be useful to provide improved sensors which overcomeone or more of such disadvantages.

§2. SUMMARY OF THE INVENTION

Embodiments consistent with the present invention can leverage specificionic interactions with a sensing material that is electrically coupledwith the floating gate of a floating gate ion sensitive field effecttransistor (FGISFET) to sense a target material. For example, an FGISFETcan use (e.g., previously demonstrated) ionic interaction-based sensingtechniques with the floating gate of double gate (i.e., floating gateand control gate) field effect transistors. The floating gate serves asa probe and an interface to convert chemical and/or biological signalsto electrical signals, which can be measured by monitoring the change inthe device's threshold voltage, V_(T).

§3. BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts a conventional ion sensitive field effect transistor(ISFET) submerged in gas or analyte.

FIG. 2 depicts a conventional conducting polymer-based ISFET exposed togas or analyte.

FIG. 3 illustrates a cross sectional view of an exemplary floating gateion sensitive field effect transistor (FGISFET) that is consistent withthe present invention.

FIG. 4 illustrates a cross sectional view of a conventional field effecttransistor.

FIG. 5 illustrates a cross sectional view of a conventional floatinggate field effect transistor.

FIG. 6 illustrates a cross sectional side view of an exemplary floatinggate ion sensitive field effect transistor that is consistent with thepresent invention.

FIGS. 7A and 7B illustrate a cross sectional front view and a plan view,respectively, of an exemplary floating gate ion sensitive field effecttransistor that is consistent with the present invention.

FIG. 8 is a flow diagram of an exemplary method that may be used toperform target sensing with an ISFET exposed to a sample, in a mannerconsistent with the present invention.

FIG. 9 illustrates an exemplary double ISFET sensor with a differentialamplifier-based read-out circuit for generating a signal correspondingto voltage shifts (e.g., threshold voltage shifts) in a mannerconsistent with the present invention.

FIG. 10 illustrates a cross sectional side view of an exemplary doubleISFET component, consistent with the present invention, which may beused in the exemplary double ISFET arrangement of FIG. 9.

FIG. 11 flow diagram of an exemplary method that may be used todetermine the presence, amount, and/or concentration of a targetmaterial using a double ISFET sensor with a differential amplifier basedread-out circuit in a manner consistent with the present invention.

FIG. 12 depicts the chemical structure of an aniline trimer used as asensing material in an exemplary embodiment consistent with the presentinvention.

FIG. 13 is a chart depicting √{square root over (I_(DS))} versus V_(GS)characteristics of an exemplary FGISFET biased in saturation region, andindicating the initial threshold voltage.

FIG. 14 is a chart depicting √{square root over (I_(DS))} versus V_(GS)characteristics of an exemplary FGISFET with an aniline trimer as asensing material and the FGISFET with an aniline trimer as a sensingmaterial exposed to ammonium, along with the indicated thresholdvoltages.

FIG. 15 illustrates an array of FGISFETs with peripheral circuitry thatmay be used for detecting multiple targets and/or minimizing errors.

FIG. 16 illustrates a schematic diagram of an exemplary ISFET elementconsistent with the present invention, which may be used in an arraysuch as the one depicted in FIG. 15.

FIG. 17 illustrates a schematic diagram of exemplary shift measurementcircuitry, consistent with the present invention, which may be used inan array such as the one depicted in FIG. 15.

§4. DETAILED DESCRIPTION

The present invention may involve novel methods, apparatus, compositionsof matter, and combinations for chemical and/or biological sensing usinga floating gate (e.g., ion sensitive) field effect transistor. Thefollowing description is presented to enable one skilled in the art tomake and use the invention, and is provided in the context of particularapplications and their requirements. Thus, the following description ofembodiments consistent with the present invention provides illustrationand description, but is not intended to be exhaustive or to limit thepresent invention to the precise form disclosed. Various modificationsto the disclosed embodiments will be apparent to those skilled in theart, and the general principles set forth below may be applied to otherembodiments and applications. For example, although a series of acts maybe described with reference to a flow diagram, the order of acts maydiffer in other implementations when the performance of one act is notdependent on the completion of another act. Further, non-dependent actsmay be performed in parallel. As another example, different sensingmaterials or types of sensing materials may be used, in electricallyconductive connection with a floating gate electrode, to sense differenttargets or types of targets. No element, act or instruction used in thedescription should be construed as critical or essential to the presentinvention unless explicitly described as such. Also, as used herein, thearticle “a” is intended to include one or more items. Where only oneitem is intended, the term “one” or similar language is used. Thus, thepresent invention is not intended to be limited to the embodiments shownand the inventors regard their invention as any patentable subjectmatter described.

§4.1 FIRST EMBODIMENT

FIG. 3 illustrates a cross sectional view of an exemplary floating gateion sensitive field effect transistor 300 (FGISFET), consistent with thepresent invention, that overcomes at least some of the limitations ofconventional and organic ISFETs introduced in § 1.2 above. The exemplaryFGISFET 300 may comprise a substrate 310 (which may be silicon-based ororganic, for example, though is preferably not organic), a source 320, adrain 330, a first insulating layer (e.g., an oxide layer) 340, afloating gate 342, a second insulating layer (e.g., an oxide layer) 344,a sensing material 348 and a control gate 346. The control gate 346 maybe used for setting the sensor's operating point and the floating gate342 may be used to measure ionic activity associated with a targetmaterial. The sensing material 348 may be an ion-sensitive material thatmay be selected to sense a specific chemical, a specific class ofchemicals, a specific biological material, and/or a specific class ofbiological materials. Although the sensing material 348 is shown asbeing arranged on (e.g., deposited on) the floating gate 342, it may bearranged on some other conductive surface which is electrically coupledwith the floating gate 342.

The device structure may be similar to that of a floating gate FET whichis widely used for EPROM or Flash memory. (See, e.g., S. M. Kang and Y.Leblebici, CMOS Digital Integrated Circuits, Third Edition, McGraw Hill(2002), incorporated herein by reference.) In a floating gate FET,threshold voltage (i.e., the gate voltage required to induce minoritycarriers at the oxide-silicon interface) is determined by the differencein work function between the floating gate 342 and substrate 310 and theamount of charges injected or trapped on the floating gate 342. Thesensing material 348 may be an ion-sensitive material and may modify thethreshold voltage. The threshold voltage can be modified (i) after theapplication of sensing material, such as polyanaline, on floating gatedue to its ionic charge (referred to as “doping”) characteristics; (ii)during the sensing process due to the binding (or some otherinteraction) of target material (such as ammonia) with sensing materialand the de-doping of sensing material; and/or (iii) during the sensingprocess due to the binding (or some other interaction) of targetmaterial with sensing material and consequent change of ionic charge ofthe sensing material, etc.

Unlike conventional silicon-based ISFETs, the control gate 346 voltagecan be set directly to a desired value for optimum sensitivity anddynamic range. The FGISFETs are suitable for sensing analytes, gases,etc. In addition, the FGISFET can be miniaturized, and integrated withon-chip bias, read out, and/or signal processing circuits. The exemplaryFGISFET may also benefit from technology scaling that has revolutionizedthe semiconductor industry. Potentially, millions of such FGISFETs canbe fabricated on a single chip and structured in a way similar to anarray of complementary field effect transistor (CMOS) or charge coupleddevice (CCD) based image sensors, which are commonly used in digitalcameras. Thus, the FGISFET can provide a basis for low-cost,miniaturizable and portable solutions to chemical and/or biologicalsensors.

Thus, embodiments consistent with the present invention can leveragespecific ionic interactions with a sensing material 348 electricallycoupled with the floating gate 342 of a floating gate based ionsensitive field effect transistors (FGISFET) 300 to sense a targetmaterial. In recent work on chemical sensors, a surface imprintingmethod has been developed, which creates cavities on the ion sensitiveelectrode (Indium Tin Oxide (ITO)). This method has been applied forsensing various chemical agents. In parallel, research on biologicalsensors have screened a vast variety of ligands, which interact withbacterial spores and created a library of these specific ionic ligands,which include antibodies, aptamers, lectins, heptapeptides and sugars,and also synthetic ionic molecules (See, e.g., K. Levon, B. Yu,“Development of Multivalent Macromolecular Ligands for EnhancedDetection of Biological Targets,” submitted to IUPAC PC Symposium Seriesand the utility and provisional patent applications listed in § 4.4below.)

The exemplary FGISFET 300 can use (e.g., previously demonstrated) ionicinteraction-based sensing techniques with the floating gate of doublegate (i.e., floating gate and control gate) field effect transistors.The floating gate serves as a probe and an interface to convert chemicaland/or biological signals to electrical signals, which can be measuredby monitoring the change in the device's threshold voltage, V_(T).

§ 4.1.1 FET Design

FIG. 4 illustrates a cross sectional view of a conventional field effecttransistor 400. A typical field effect transistor 400, as shown in FIG.4 is a four terminal device, fabricated in either n-type or p-typesilicon substrate (B) 410. These four terminals are source (S) 420,drain (D) 430, gate (G) 440, and bulk/substrate (B) 410. An insulatinglayer (e.g., an oxide layer) 450 is arranged between the gate and thesubstrate 410. The gate oxide capacitance per unit area is depicted with460 and does not imply a physical capacitor as part of a FET.

The gate 440 electrode controls the amount of charges flowing betweensource 420 and drain 430. In the case of an n-type FET (nFET), if thevoltage difference between gate 440 and source 420 (V_(GS)) is higherthan a threshold voltage (V_(T)), a conductive channel is formed in thesubstrate 410 between source 420 and drain 430. By applying a positivedrain-to-source voltage (V_(DS)), current flow is established betweendrain 430 and source 420 terminals. The conductivity of the channel (ordrain current) is controlled by gate-to-source and drain-to-sourcevoltages, as well as material properties and dimensions of the substrate410 and gate electrode 440.

The threshold voltage of a field effect transistor is determined by thedifference in work function between the gate electrode 440 and siliconsubstrate 410, material and physical properties of the oxide layer 450located between the gate electrode 440 and channel (substrate region 410between the source 420 and drain 430), and the interfacialcharacteristics of gate oxide. The threshold voltage of a single-gatefield effect transistor (V_(T) ^(SG)) is given by:

$V_{T}^{SG} = {\Phi_{GC} - {2\varphi_{F}} - \frac{Q_{B}}{C_{OX}} - \frac{Q_{OX}}{C_{OX}}}$

where Φ_(GC) is the difference in work function between gate 440 andchannel, 2Φ_(F) is substrate Fermi potential, Q_(B) is the depletionregion charge density, Q_(OX) is Si—SiO₂ interface charge density, andC_(OX) is the gate oxide capacitance per unit area.

FIG. 5 illustrates a cross sectional view of a conventional floatinggate field effect transistor 500. The floating gate FET 500 in generalhas many commonalities to a regular FET and its operation is similar toa regular FET. Specifically, the floating gate FET 500 may comprise asubstrate (B) 510, a source (S) 520, a drain (D) 530, an insulatinglayer (e.g., an oxide layer) 550, a floating gate (e.g., highly dopedpolysilicon) 540, another insulating layer (e.g., a second oxide layer)542, and a control gate (G) (e.g., highly doped polysilicon) 544. Thefloating gate-oxide capacitance per unit area is depicted by element570, and the capacitance per unit area between the control gate andfloating gate is depicted by element 560. Note that elements 560 and 570do not imply physical capacitors as part of a floating gate FET.

The threshold voltage V_(T) ^(FG) of the FGFET 500 is given by:

$V_{T}^{FG} = {{\frac{C_{OX} + C_{FG}}{C_{FG}}V_{T}^{SG}} - \frac{Q_{FG}}{C_{FG}}}$

where C_(FG) is the capacitance per unit area between the control andfloating gates, Q_(FG) is the net charge on floating gate 540.

If ion-sensitive sensing material is applied to the floating gate 540,as a result of its ionic response to specific targets, there is a netchange in the value of Q_(FG). This net change can be determined bymeasuring the shift in V_(T) ^(FG). In other words, the shift in V_(T)^(FG) is directly related to the detection of a specific target.Further, the extent of the V_(T) ^(FG)-shift may be related to theamount, strength, and/or concentration of the target. In the saturationregion of operation of a long channel MOSFET, the drain current is givenby:

$I_{DS} = {\frac{\mu \; C_{OX}}{2}\frac{W}{L}\left( {V_{GS} - V_{T}} \right)^{2}}$

where μ is the mobility of the carriers, and W/L is the width/lengthratio of the field effect transistor. By plotting √{square root over(I_(DS))} versus V_(GS), the x-axis intercept, V_(T), can be determined.There are also other sophisticated techniques that can be used toestimate the value of threshold voltage. (See, e.g., K. Terada, K.Nishiyama, K. I. Hatanaka, “Comparison of MOSFET-threshold voltageextraction methods,” Solid State Electronics, vol. 45, pages 35-40(2001), incorporated herein by reference.)

§ 4.1.2 FET Fabrication

FIGS. 7A and 7B illustrates a cross sectional front view and plan view,respectively, of an exemplary floating gate ion sensitive field effecttransistor that is consistent with the present invention. The FGISFET700 is similar in operation to the FGISFETs described above, withreference to FIG. 3. In particular, the FGISFET 700 may comprise asubstrate 710, an oxide layer 740, a source 720, a drain 730, a firstfloating gate 750, another oxide layer 752, a control gate 754, adialectic (e.g., SiO₂ insulator) 760, a first metal layer 762, anotherdielectric 764, a second metal layer 770, and a glass cover 780.

The FGISFET 700 may be fabricated using standard CMOS process—using a2-polysilicon and 2-metal layer 1.2 μm process technology. Unlikeconventional floating gate devices, used from EPROM or flash memory, thefloating gate of an ISFET is electrically coupled with a receptor on asecond metal layer 770. Generally, in 1.2 μm process technology, thesecond metal layer is encapsulated in glass, and the protective glasscoating at chip periphery is etched to expose the bonding pads to createbond wire connections for packaging. In this design, the glass coatingis also etched in selective locations to expose the second metal layer770 receptors, connected to the floating gate 750. The exposed secondmetal layer 770 surface can be spin-coated with ion-sensitive materialsfor chemical and/or biological sensing.

Due to antenna effects, the floating gate 750 can collect positive ornegative charges during plasma processing, and it might eventuallycreate a high electric field within the gate oxide, leading to oxidebreakdown. To avoid the consequences of antenna effects duringfabrication, the floating gate 750 may be tied to the silicon substrate710 ground terminal using a second metal layer 770 interconnect, therebyproviding a discharge path for any accumulated charges on the floatinggate 750. After the completion of all fabrication steps, the secondmetal layer 770 interconnect may be rendered non-functional (e.g., bycutting it with a focused laser beam), at which point the ISFET becomesfunctional. Instead of a single top gate, multiple top gates can beintegrated to adjust the threshold voltage of ISFETs and improve theiryield.

FIG. 6 is a cross sectional side view which illustrates the electricalcoupling of the floating gate 615 with a second metal layer 640, via afirst conductor (e.g., wire) 625, first metal layer 630, and a secondconductor (e.g., wire) 635. Also shown are glass 645, control gate 620,bulk substrate 605, and source (or drain) 610. As described above withreference to FIGS. 7A and 7B, sensing material (not shown) may beapplied to the second metal layer.

§ 4.1.3 Method(s) of Use

FIG. 8 is a flow diagram of an exemplary method 800 that may be used toperform target sensing with an FGISFET exposed to a sample, in a mannerconsistent with a first embodiment of the present invention. Thethreshold voltage of an FGISFET having sensing material is determined ata first time (before the FGISFET is exposed to a sample). (Block 810)Next, the FGISFET having sensing material is exposed to a sample thatmay contain a target material (e.g., gases (ammonia), chemicals,biological material (DNA, cellular activities), etc) and its thresholdvoltage is determined at a second time after such exposure. (Block 820)The two threshold voltages obtained by the same FGISFET are compared.(Block 830) For example, a threshold voltage shift may be discovered.Using this comparison (and perhaps other information) a presence,amount, and/or concentration of a target (if any) may be determined(Block 840) before the method 800 is left (Node 850).

Referring back to blocks 810 and 820, the threshold voltages may bedetermined using √{square root over (I_(DS))} versus V_(GS) plots, wherethe threshold voltage is simply located at the x-axis intercept, ordetermined using some other method. Using these plots shifts inthreshold voltage may be determined.

Referring back to block 840, the voltage shift (if any), resulting fromthe ionic interactions between the sensing material (deposited on, or inelectrical conduction with, the floating gate) and the sample, may betranslated to material properties such as concentration, toxicity,amount, presence/absence, etc. For example, the voltage shift may betranslated into a material property using a calibrated look-up table.

§ 4.2 SECOND EMBODIMENT § 4.2.1 Threshold Voltage Measuring Circuit

FIG. 9 illustrates an exemplary differential amplifier-based read-outcircuit 900 for measuring threshold voltage shifts in a mannerconsistent with the present invention. The circuit 900 may include adifferential amplifier 950 for outputting a voltage differential, anFGFET 910 with sensing material, an FGFET 920 without sensing material,resistors 930, 940 and an analog-to-digital converter 960.

The differential amplifier 950 can output a signal representing athreshold voltage difference between the two FGFETs 910 and 920. Theamplified threshold voltage differential signal may be provided as aninput to an analog-to-digital converter 960. Lines 970 may provide thedigitized signal to a signal processing system (not shown) fortranslation of the signal to a target material property (e.g., presence,absence, amount, concentration, toxicity, etc.) measurement.

FIG. 10 illustrates a cross sectional side view of an exemplary doubleISFET component 1000, consistent with the present invention, which maybe used in the exemplary circuit 900 of FIG. 9. The component 1000 mayinclude a common or shared (e.g., Si) substrate 1002. The left FGFET issimilar to that 600 described with reference to FIG. 6. The left FGFETmay include a floating gate 1011, a source (or drain) 1006, a drain (orsource) 1004, a control gate 1013, a first metal layer 1014 and a secondmetal layer 1016. A first conductor (wire) 1012 may electrically couplethe floating gate 1011 with the first metal layer 1014, and a secondconductor (wire) 1015 may electrically couple the first metal layer 1014with the second metal layer 1016. The second metal layer 1016 may have asensing material (not shown) on it, which may be exposed to theenvironment (e.g., not enclosed in glass 1085). The right FGFET mayserve to provide a control (i.e., comparison) signal. The right FGFETmay include a floating gate 1021, a source (or drain) 1008, a drain (orsource) 1010, a control gate 1023, a first metal layer 1024 and a secondmetal layer 1026. A first conductor (wire) 1022 may electrically couplethe floating gate 1021 with the first metal layer 1024, and a secondconductor (wire) 1025 may electrically couple the first metal layer 1024with the second metal layer 1026. The second metal layer 1026 may beisolated from the environment (e.g., enclosed by glass 1085), althoughthis is not necessary. In some applications, it may be preferable toexpose the second metal layer 1026 to the environment (e.g., notenclosed in glass 1085).

As shown, the sources (or drains) 1006 and 1008 may be electricallycoupled (e.g., share a common terminal). In this regard, metal 1084 maybe coupled with both 1006 and 1008 via conductors (e.g., wires) 1080 and1082. Although not shown, the control gates 913 and 923 may also beelectrically coupled, in which case the same biasing voltage source maybe shared.

§ 4.2.2 Methods of Use

FIG. 11 is a flow diagram of an exemplary method 1100 that may be usedto perform target sensing using a differential amplifier based read-outcircuit, such as that shown in FIGS. 9 and 10 for example, in a mannerconsistent with the present invention. The threshold voltages of a firstFGFET (without sensing material) and of a second FGFET (with sensingmaterial) are obtained. (Blocks 1110 and 1120) Subsequently, thedifference of the threshold voltages of the first and second FGFETs isdetermined. (Block 1130) The threshold voltage difference may beamplified by an amplifier and converted into a digital signal by ananalog-to-digital converter. (Blocks 1140 and 1150) The (e.g., digital)signal may then be analyzed to determine a presence, amount, and/orconcentration of a target (if any) (Block 1160), before the method 1100is left (Node 1170).

Referring to blocks 1110,1120, and 1130, a differential amplifier-basedcircuit, such as the one depicted in FIG. 9 for example, may be used toobtain the threshold values of the first and second FGFETs and determinethe threshold voltage difference of the two FGFETs. Of course, othermethods of obtaining threshold voltages are possible and may be used.

§ 4.3 Experimental Results

Extensive measurements and characterization of a test chip have beenperformed to demonstrate key concepts of the FGISFET. These measurementsindicate that it is feasible to coat the floating gate with sensingmaterials within a small (e.g., 200 μm×200 μm) region and their ionicproperties are reflected by a shift in the device's threshold voltage.In one of the test cases, an aniline trimer has been used as the sensingmaterial, which is a 3-benezene ring structure 1200 as shown in FIG. 12.At the Nitrogen (N) binding site, dopants can be incorporated to havespecificity to a particular chemical, a particular class of chemicals, aspecific biological material, or specific class of biological materials(e.g., pollutants, toxic chemicals, biological agents such as Bacillusanthracis, etc.). The aforementioned material 1200 was used as a sensingmaterial to demonstrate the operation of such an FGISFET exposed to thetarget ammonia.

FIG. 13 is a chart depicting √{square root over (I_(DS))} versus V_(GS)characteristics of a FGISFET biased in saturation region, and indicatingthe initial threshold voltage of the FGISFET without the sensingmaterial (aniline trimer). This chart depicts the initialcharacteristics of the floating gate ISFET without sensing materialbiased in saturation region. The x-axis intercept indicates the initialthreshold voltage.

FIG. 14 is a chart depicting √{square root over (I_(DS))} versus V_(GS)characteristics of a FGISFET with an aniline trimer as a sensingmaterial without exposure to the (70 ppm) ammonium target 1410, and theFGISFET with an aniline trimer as a sensing material exposed to theammonium target 1420. FIG. 14 also shows the threshold voltages (about4.2 V and 5.25 V). Again the x-axis intercepts indicate the thresholdvoltages. This chart depicts measurements of the same I-Vcharacteristics as in FIG. 13.

FIGS. 13 and 14 illustrate preliminary experimental results of V_(T)^(FG) shift when the floating gate of an nFET is coated with anilinetrimer. Due to net negative charge concentration in the floating gate,there is a positive shift in V_(T) ^(FG). (Compare plot of FIG. 13 withplot 1410 of FIG. 14.) As the floating gate, coated with aniline trimer,is exposed to ammonia, there is an additional shift in device thresholdvoltage due to the de-doping of the sensing materials. (Compare plots1410 and 1420.)

§ 4.4 Extensions and Refinements

Embodiments consistent with the present invention can detect multipletargets, such as different types of gases and/or bacteria. Embodimentsconsistent with the present invention can reduce false alarms. In bothcases, an array of FGISFETs may be used. A high-level block diagram ofsuch FGISFET based system 1500, with a 4×4 array of ISFETs isillustrated in FIG. 15. Specifically, such a system 1500 may include apower management circuit (not shown), circuits for measuring thresholdvoltage shifts (and perhaps performing additional signal processing)1510, a bias circuit 1540, an array of FGISFETs 1530, and lines 1520 forthe application of row selection signals.

FIG. 16 illustrates a schematic diagram of an exemplary ISFET element1630 consistent with the present invention, which may be used in anarray such as the one depicted in FIG. 15. Line 1520 a for applicationof row selection signal may be used to control switch 1632. A biasvoltage V_(B) is applied to the control gate of FGISFET 1634, whichincludes sensing material. Current flows from bias circuit (not shown)are also shown.

FIG. 17 illustrates a schematic diagram of exemplary shift measurementcircuitry 1710, consistent with the present invention, which may be usedin an array such as the one depicted in FIG. 15 and with an element 1630such as the one depicted in FIG. 16. The circuitry 1710 includes an(e.g., matched) FGISFET 1712 without sensing material, differentialamplifier 1714 and resistors 1716, 1718.

In at least some embodiments consistent with the present invention, theperipheral circuits of the FGISFET array may be similar to those ofconventional static or dynamic memory, CMOS/CCC imagers, etc. Forexample, referring back to FIG. 15, in an array configuration, the V_(T)^(FG) shift of all FGISFETs within the same row may be measuredsimultaneously by enabling their word line 1530. One by one all wordlines 1530, one word line at any time, may be enabled and measurementsof V_(T) ^(FG) shift for the entire array is completed. A calibratedlook-up table can be used to convert the electrical signals to materialproperties such as concentration, toxicity, amount, presence/absence,etc. of the sensed target. During this phase, spatial correlation andadvanced signal processing may be performed to improve the integrity ofmeasured signals and to reduce false alarm rate.

Alternatively, or in addition, the use of integrated array of FGISFETscan be used to facilitate the detection of multiple targetssimultaneously since different individual FGISFETs or different groupsof FGISFETs can be made selective to different targets by applyingappropriate sensing materials to their floating gates.

In addition to readout circuits, a power management unit can beintegrated to switch off the power supplies when the FGISFET array isnot in data acquisition mode. Such features are useful if the sensorarray is to be deployed for environmental monitoring where it isdesirable to conserve energy to extend battery life.

Various targets can be sensed by selecting the appropriate sensingmaterial to be provided. For example, although experiments illustratingthe operation of the present invention used aniline trimer to detectammonium, various other sensing materials can be incorporated inFGISFET(s) to sense various other target materials. Generally, thesesensing-target combinations display ionic behavior when the target binds(or otherwise interacts with, or comes into contact with) the sensinglayer. For example, Table 1 lists potential sensing materials for use onFGISFET based applications.

TABLE I Sensing Material Target Application Polyaniline DNA DNA SensorAniline Ammonia Gas Sensor Pheochromocytoma cells Cellular ActivitiesCell-Base Sensor (PC12)

With appropriate synthesis, selection, and integration of sensingmaterial, the FGISFET can be used to detect moisture, temperature,bacterium, DNA, protein, polymer, acids, gas or chemical solutions.Publicly available or proprietary techniques may be used for synthesisand integration of the sensing material. For example, covalent couplingmay be use to immobilize the sensing material (also referred to as a“ligand”) to the gate. Depending on the available reactive groups,amine, thiol and aldehyde coupling chemistries may be used.Immobilization techniques providing a more unidirectional ligand, suchas streptavidin-biotin, may also be used. Different immobilizationtechniques are sometimes preferred for different types of ligands (suchas acidic, base, or neutral peptides/proteins, nucleic acids,polysaccharides, of NH2, SH, COOH, CHO functional groups, etc.). U.S.(Utility and Provisional) patent application Ser. Nos.:

-   -   10/170,903, titled “CHIRAL LIGAND EXCHANGE POTENTIOMETRY AND        ENANTIOSELECTIVE SENSORS,” filed on Jun. 13, 2002;    -   10/242,590, titled “SURFACE IMPRINTING: INTEGRATION OF MOLECULAR        RECOGNITION AND TRANSDUCTION,” filed on Sep. 12, 2002;    -   60/486,088, titled “BACTERIAL BIOSENSOR,” filed on Jul. 10,        2003;    -   10/888,342, titled “BIOSENSOR AND METHOD OF MAKING SAME,” filed        on Jul. 9, 2004;    -   10/888,530, titled “BACTERIAL BIOSENSORS,” filed on Jul. 9,        2004;    -   10/719,688, titled “GLYCOCONJUGATE SENSORS,” filed on Nov. 21,        2003; and    -   60/556,231, titled “IONIC BASED SENSING FOR IDENTIFYING GENOMIC        SEQUENCE VARIATIONS AND DETECTING MISMATCH BASE PAIRS, SUCH AS        SINGLE NUCLEOTIDE POLYMORPHISMS,” filed on Mar. 25, 2004,        describe immobilization techniques and/or sensing        material-target material combinations that may be used. Each of        these applications is incorporated herein by reference.

§ 4.5 Conclusions

In view of the foregoing, the present invention allows a reliable methodfor chemical and/or biological sensing using one or more floating gateISFETs. At least some of these sensors can be minimized. At least someof these sensors can be used to detect charge changes (e.g., ion loss orgain) when a sensing material comes into contact with a target material.Such sensors have the potential to add tremendous value to our society,for example by aiding in the protection of our environment, cities,bridges, and tunnels from toxic gases or harmful biological agents.

1. A method for determining the presence or concentration of a targetmaterial in a medium, the method comprising: a) determining acurrent-voltage characteristic of a floating gate field effecttransistor having a floating gate electrically coupled with a sensingmaterial having a charge that changes in the presence of the targetsubstance; and b) determining a presence or concentration of the targetsubstance based on the determined current-voltage characteristic.
 2. Themethod of claim 1 wherein the current-voltage characteristic is athreshold voltage of the floating gate field effect transistor.
 3. Themethod of claim 1 wherein the act of determining a presence orconcentration of a target substance includes comparing the determinedcurrent-voltage characteristic with another current-voltagecharacteristic.
 4. The method of claim 3 wherein the othercurrent-voltage characteristic is one determined from the floating gatefield effect transistor before it is applied to the medium.
 5. Themethod of claim 3 wherein the other current-voltage characteristic isone determined from another floating gate field effect transistor havinga floating gate that is not electrically coupled with a sensing materialhaving a charge that changes in the presence of the target substance. 6.The method of claim 5 wherein the other floating gate field effecttransistor has components that substantially match those of the floatinggate field effect transistor.
 7. The method of claim 5 wherein the actof comparing the determined current-voltage characteristic with anothercurrent-voltage characteristic includes providing a first voltage and asecond voltage to inputs of differential amplifier.
 8. The method ofclaim 1 further comprising applying a predetermined voltage to thecontrol gate of the floating gate field effect transistor, wherein thepredetermined voltage is selected to place the floating gate fieldeffect transistor into its optimum operating range.
 9. Apparatus fordetermining the presence or concentration of a target material in amedium, the apparatus comprising: a) means for determining acurrent-voltage characteristic of a floating gate field effecttransistor having a floating gate electrically coupled with a sensingmaterial having a charge that changes in the presence of the targetsubstance; and b) means for determining a presence or concentration ofthe target substance based on the determined current-voltagecharacteristic.
 10. The apparatus of claim 9 wherein the current-voltagecharacteristic is a threshold voltage of the floating gate field effecttransistor.
 11. The apparatus of claim 9 wherein the means fordetermining a presence or concentration of a target substance includemeans for comparing the determined current-voltage characteristic withanother current-voltage characteristic.
 12. The apparatus of claim 11wherein the other current-voltage characteristic is one determined fromthe floating gate field effect transistor before it is applied to themedium.
 13. The apparatus of claim 11 wherein the other current-voltagecharacteristic is one determined from another floating gate field effecttransistor having a floating gate that is not electrically coupled witha sensing material having a charge that changes in the presence of thetarget substance.
 14. The apparatus of claim 13 wherein the otherfloating gate field effect transistor has components that substantiallymatch those of the floating gate field effect transistor.
 15. Theapparatus of claim 11 wherein the means for comparing the determinedcurrent-voltage characteristic with another current-voltagecharacteristic include means for providing a first voltage and a secondvoltage to inputs of differential amplifier.
 16. The apparatus of claim9 further comprising means for applying a predetermined voltage to thecontrol gate of the floating gate field effect transistor, wherein thepredetermined voltage is selected to place the floating gate fieldeffect transistor into its optimum operating range.